Side population cells as prototype of chemoresistant, tumor-initiating cells

Abstract

Classically, isolation of CSCs from tumors exploits the detection of cell surface markers associated with normal stem cells. Invariable expression of these cell surface markers in almost all proliferating tumor cells that albeit impart specific functionality, the universality, and clinical credibility of CSC phenotype based on markers is still dubious. Side Population (SP) cells, as defined by Hoechst dye exclusion in flow cytometry, have been identified in many solid tumors and cell lines and the SP phenotype can be considered as an enriched source of stem cells as well as an alternative source for the isolation of cancer stem cells especially when molecular markers for stem cells are unknown. SP cells may be responsible for the maintenance and propagation of tumors and the proportion of SP cells may be a predictor of patient outcome. Several of these markers used in cell sorting have emerged as prognostic markers of disease progression though it is seen that the development of new CSC-targeted strategies is often hindered by poor understanding of their regulatory networks and functions. This review intends to appraise the experimental progress towards enhanced isolation and drug screening based on property of acquired chemoresistance of cancer stem cells.

Figure 1

“Side population” phenotype in an oral squamous cell carcinoma cell line, RCB1015. The cell line was stained with Hoechst33342 and analyzed by flow cytometry. (SP-side population; MP-main population; bf-bright field image; uv-ultraviolet fluorescence; blue color- nuclear staining with Hoechst33342 dye).

Figure 2

Prime instigators for chemoresistance in tumor stem cells. Factors contributing to acquired chemoresistance in cancer stem cells epitomized by side population phenotype across multiple tumor types.